KINETICS OF HEPATOCYTE GROWTH FACTOR-INDUCED DNA-SYNTHESIS INVITRO - A COMPARATIVE-STUDY WITH EPIDERMAL GROWTH-FACTOR AND INSULIN

被引:1
作者
WOODMAN, AC [1 ]
COLLARD, J [1 ]
SELDEN, C [1 ]
HODGSON, HJF [1 ]
机构
[1] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT MED,GASTROENTEROL UNIT,DU CANE RD,LONDON W12 0NN,ENGLAND
关键词
HEPATOCYTE GROWTH FACTOR; EPIDERMAL GROWTH FACTOR; HEPATOCYTE CULTURES; CELL KINETICS; DNA SYNTHESIS;
D O I
10.1097/00042737-199306000-00010
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objective: To describe the kinetics of in vitro hepatocyte proliferation induced by a range of doses of hepatocyte growth factor (HGF) compared with those seen with epidermal growth factor (EGF). Hepatocyte growth factor with/without insulin, or EGF with insulin, were added to primary rat hepatocytes 20 h after plating. Methods: The cumulative fraction of cells with nuclear labelling following the addition of H-3-thymidine was determined by autoradiography at intervals from 32-66 h. Results: Several cell cycle parameters were determined. Hepatocyte growth factor and EGF were shown to have identical pre-replicative lag times (17 h) at all doses. Entry of hepatocytes into DNA synthesis after stimulation with HGF obeyed first order kinetics, as does entry after ECF stimulation. The maximal rate constant for the rate of entry into DNA synthesis (kG1/S) was significantly greater for HCF (0.0229/h) and HGF with insulin (0.0275/h) than EGF with insulin (0.0194/h; P<0.005). Conclusion: Hepatocyte growth factor acts as a strong proliferative stimulus at the G1 to S interface, compatible with the hypothesis that it is a major physiological stimulus to liver regeneration.
引用
收藏
页码:451 / 456
页数:6
相关论文
共 28 条
[1]  
Alison M.R., Regulation of hepatic growth, Physiol Rev, 66, pp. 499-541, (1986)
[2]  
Michalopoulos G.K., Liver regeneration: Molecular mechanisms of growth control, FASEB J, 4, pp. 176-187, (1990)
[3]  
Shing Y., Folkman Y.S., Sullivan R., Butterfield C., Murrey J., Klagsburn M., Heparm-affinity: Purification of a tumor derived capillary endothelial cell growth factor, Science, 223, pp. 1296-1299, (1984)
[4]  
Zarnegar T., Michalopoulos G.K., Purification and biological characterisation of human hepatopoeitin A, a polypeptide growth factor for hepatocytes, Cancer Res, 49, pp. 3314-3320, (1989)
[5]  
Kan M., Huan J., Mansson P., Yasumttsu H., Carr B., McKeehan W., Heparin-binding growth factor type 1 (Acidic fibroblast growth factor): A potential biphasic autocrine and paracrine regulator of hepatocyte regeneration, Proc Natl Acad Sci, 6, pp. 7432-7436, (1989)
[6]  
Bucher N., Patel U., Cohen S., Hormonal factors and liver growth, Adv Enzyme Reg, 16, pp. 205-213, (1977)
[7]  
Nakamura T., Nawa K., Icmhara A., Partial purification and characterisation of a hepatocyte growth factor from serum of hepatectomised rats, Biochem Biophys Res Commun, 122, pp. 1450-1459, (1984)
[8]  
Selden A.C., Johnson R Darby H., Gupta S., Hodgson H., Human serum dose contain a high molecular weight hepatocyte growth factor: Studies pre- and post-hepatic resection, Biochem Biophys Res Commun, 139, pp. 361-366, (1986)
[9]  
Nakamura T., Nisheawa T., Higiya M., Seki T., Shimonishi M., Sugimura A., Et al., Molecular cloning and expression of human hepatocyte growth factor, Nature, 342, pp. 440-443, (1989)
[10]  
Kinoshita T., Tashiro K., Nakamura T., Marked increase of HGF mRNA in non-parenchymal liver cells of rats treated with hepatotoxins, Biochem Biophys Res Commun, 165, 3, pp. 1229-1234, (1989)